Erythrocyte enzymopathies associated with low or unstable glutathione probably are the most frequent of the inherited erythrocytic diseases. Clinically, their symptoms range from drug-induced hemolytic anemia to congenital nonspherocytic hemolytic disease. The objective of this project is to study glutathione-deficiency in canine and ovine erythrocytes as models for human diseases related to abnormal glutathione metabolism. The glutathione turnover rate and uptake of the precursor amino acids for glutathione synthesis will be studied in glutathione-deficient Alaskan Malamute dogs. Because glutathione-deficiency in dogs is accompanied by an abnormal erythrocyte shape (stomatocytosis), the cation movements and in vivo turnover of certain erythrocyte membrane proteins will be measured. Alterations in membrane protein during an "oxidant" stress will be studied using glutathione-deficient (gamma-glutamylcysteine synthetase-deficient) sheep. Study of animals with glutathione-deficiency should provide a better understanding of glutathione metabolism and function in red blood cells.